Bitter　taste　receptor　(TAS2R)　agonists　have　bronchodilatory　potentials.　Erythromycin　is　a　ligand　of　TAS2R10,　but　its　relaxant　profile　is　unknown.　This　study　was　performed　to　understand　the　relaxant　effects　of　erythromycin　and　its　potential　mechanism.Airway　resistance　was　tested　by　the　whole　body　plethysmography　in　the　ovalbumin-aluminum　hydroxide　induced　asthma　model　mice.　Tracheal　ring　segment　myography　was　used　to　investigate　the　isometric　tension　of　the　smooth　muscle.　The　cyclic　adenosine　monophosphate　(cAMP)　concentration　was　measured　by　enzyme　immunoassay　kit.　Changes　in　the　calcium　influx　in　airway　smooth　muscle　cells　(ASMCs)　were　surveyed　using　a　real-time　confocal　microscopy.Erythromycin　significantly　relieved　airway　hyperreactivity　in　asthma　model　mice.　Erythromycin　relaxed　mouse　tracheal　segments　precontracted　with　carbachol,　KCl,　5-hydroxytryptamine　and　U46619,　and　further　dilated　the　tracheal　rings　relaxed　by　isoprenaline　or　atropine.　Epithelium　removal,　indomethacin　or　NS-398　partially　reduced　the　relaxation.　U73122,　2-APB,　iberiotoxin　or　ouabain　did　not　change　the　concentration-relaxation　curves　of　erythromycin　on　tracheal　segments.　Erythromycin　didn＇t　elevate　cAMP　level.　CaCl＜sub＞2＜/sub＞-induced　contraction　in　the　K＜sup＞+＜/sup＞-rich　solution　was　impaired　by　erythromycin　in　the　Ca＜sup＞2+＜/sup＞-free　solution.　The　intercellular　Ca＜sup＞2+＜/sup＞　level　in　the　ASMCs　was　decreased　by　erythromycin,　which　was　partly　inhibited　by　Bay　K8644　but　not　gallein.Erythromycin　had　marked　bronchodilatory　effect.　The　relaxation　might　be　related　to　the　L-type　voltage-dependent　calcium　channel,　but　not　the　gustducin-associated　βγ/phospholipase-Cβ/inositol　1,4,5-tri-phosphate　receptor/large　conductance　Ca＜sup＞2+＜/sup＞-activated　K＜sup＞+＜/sup＞　channel　pathway　or　a　cAMP-dependent　way.